PRIMER: Human Subjects, Past, Present,

and Future

Susan Metosky, Arizona State UniversityDebra Murphy, Arizona State University

Objectives• Overview

• Historical Perspective

• IRB at Arizona State University (ASU)

• Questions and Answers

Areas and committees supported by Office of Research Integrity and

Assurance (ORIA)

Responsible Conduct in Research

RCR

Security

Scientific DivingDCB Conflict of

InterestIPIRC

Biosafety IBC

Export Controls

Animal Care IACUC

Human Subjects

IRB

Research Integrity

and Assurance

Ensuring support for compliance with Local, State, and Federal Regulations through responsible conduct of research.

Who are our stakeholders?• Researchers • Federal Government• Participants in Research Studies• Sponsored Projects and Grants Staff• Research Administrators• Administrators at Arizona State University• Committee members

Protect researchers/university

Protect participants

Follow Regulations

ORIA’s roles

Institutional Review Board (IRB)

• Reviews all proposed research involving human subjects

• Ensures that participants are treated ethically

• Diverse membershipo At least 5 memberso Males and Femaleso One unaffiliated member

“Those who cannot remember the past are condemned to repeat it ."

- George Santayana

History

20th Century

Research

1972 Syphilis Study Exposed

1966 The Beecher Article (NEJM)

1932 Tuskegee Syphilis Study begins

Nuremberg Code 1947

Kefauver-Harris Amendments Food, Drug and Cosmetic Act 1962

Declaration of Helsinki 1964

Belmont Report 1979

Consolidated HHS/FDA Regulations 1981

Common Rule 1991

Nazi Experiments

Milgram Study

Clinton Apology 1997

Tuskegee Syphilis Study

• Images taken from: https://www.msu.edu/course/hm/546/tuskegee.htm and• http://alondranelson.wordpress.com/2012/07/25/tuskegee-and-the-black-panther-party/

Nazi War Crimes World War II

The image is from been the website: http://fcit.usf.edu/holocaust/resource/gallery/n1945.htm

Nuremberg Code (1947)• Voluntary consent• Anticipate scientific benefits• Benefits must outweigh risks• Perform animal experiments first• Avoid suffering• No intentional death or disability• Do no harm• Subjects can withdraw at any time• Investigators must be qualified• Research will stop if harm occurs

Belmont Report:

Principles and Applications

Ethical Principles Applications

Respect for Persons Informed Consent

Beneficence Assessment of risks and benefits

Justice Subject selection

Federal Regulations45CFR46

o Federal Policy for the Protection of Human Subjects

21CFR50 (Protection of Human Subjects)o Regulations about FDA-regulated clinical

investigations

21CFR56 (Institutional Review Boards)o Regulations about responsibility of IRBs that review

FDA-regulated clinical investigations

• Approval must be in place prior to initiating research activities or grant expenditure

• There are 3 types of reviews Full Board Expedited Exempt

Rules that apply to all universities

Where was ASU?

4 Federal Audits in recent years

/

Where is the ASU IRB today?

Criteria that the IRB Uses to Evaluate Protocols for Approval

• Compliance with Federal Regulations and University Policy

• No risks or risks are minimized• Acceptable risk: benefit ratio• Equitable selection of subjects• Adequate informed consent process• Privacy and confidentiality protections• Additional safeguards for vulnerable populations

Ways the ASU IRB Works to Minimize Risk

To Participants• Alternatives

o Other procedures that are less risky

• Precautionso Procedures to decrease

the likelihood that harms occur

• Safeguardso Procedures to deal

w/harms if they occur

To Researchers• Document Everything• Follow study procedures• Submit any changes to

the IRB in writingo Must be approved before

implementing

• Report unexpected events

• Ask questions

Program Enhancements at ASU• Culture of service in addition to culture of compliance

• Director and IRB Administrator serve as trained IRB alternateso Approve minor changes that do not increase risko Approve continuations that are closed to enrollment

• Exempt protocols reviewed by trained staff

• Increased emphasis on outreach

• Increase in the number of affiliation agreements

Program Enhancements at ASU• Classroom research guidance document

• Guidelines regarding subject pools

• Exempt and expedited “grid” documents

• Special review of “geographic” issues

What are some human subjects issues today?

• Gene Therapy Trials• International Research• Nanotechnology• Internet Research• Chemical and Biological Terrorism• Suspension of human subjects

programs at universities

Looking to the Future: Advanced Notice of Proposed Rule Making

Questions and Contact Information

• Debra Murphy(480) 965-2179Debra.Murphy@asu.edu

• Susan Metosky(480) 727-0871Susan.metosky@asu.edu